Autophagy impairment and lifespan reduction caused by Atg1 RNAi or Atg18 RNAi expression in adult fruit flies (Drosophila melanogaster) DOI

Mariah Bierlein,

J. B. Charles,

Trevor Polisuk-Balfour

et al.

Genetics, Journal Year: 2023, Volume and Issue: 225(2)

Published: Aug. 18, 2023

Abstract Autophagy, an autophagosome and lysosome-based eukaryotic cellular degradation system, has previously been implicated in lifespan regulation different animal models. In this report, we show that expression of the RNAi transgenes targeting transcripts key autophagy genes Atg1 or Atg18 adult fly muscle glia does not affect overall levels autophagosomes those tissues change tested flies but reduction phenotype become apparent when is expressed ubiquitously after eradicated through knockdown adipocytes. Lifespan was also observed knocked down enteroblasts midgut stem cells. Overexpression wild-type adipocytes reduces causes accumulation high ubiquitinated protein aggregates muscles. Our research data have highlighted important functions adipocytes, enteroblasts, cells their undetermined roles for regulation.

Language: Английский

Lysosomes as coordinators of cellular catabolism, metabolic signalling and organ physiology DOI
Carmine Settembre, Rushika M. Perera

Nature Reviews Molecular Cell Biology, Journal Year: 2023, Volume and Issue: 25(3), P. 223 - 245

Published: Nov. 24, 2023

Language: Английский

Citations

88
Lipid droplets and cellular lipid flux DOI

Alyssa J. Mathiowetz,

James A. Olzmann

Nature Cell Biology, Journal Year: 2024, Volume and Issue: 26(3), P. 331 - 345

Published: March 1, 2024

Language: Английский

Citations

85
Lipid droplets and polyunsaturated fatty acid trafficking: Balancing life and death DOI Creative Commons
Mauro Danielli,

Leja Perne,

Eva Jarc

et al.

Frontiers in Cell and Developmental Biology, Journal Year: 2023, Volume and Issue: 11

Published: Jan. 27, 2023

Lipid droplets are fat storage organelles ubiquitously distributed across the eukaryotic kingdom. They have a central role in regulating lipid metabolism and undergo dynamic turnover of biogenesis breakdown to meet cellular requirements for fatty acids, including polyunsaturated acids. Polyunsaturated acids esterified membrane phospholipids define fluidity can be released by activity phospholipases A

Language: Английский

Citations

69
Lipid droplets and fatty acid‐induced lipotoxicity: in a nutshell DOI Open Access

Eseiwi Obaseki,

Daniel Adebayo,

Sumit Bandyopadhyay

et al.

FEBS Letters, Journal Year: 2024, Volume and Issue: 598(10), P. 1207 - 1214

Published: Jan. 28, 2024

Lipid droplets (LDs) are fat storage organelles that conserved from bacteria to humans. LDs broken down supply cells with fatty acids (FAs) can be used as an energy source or membrane synthesis. An overload of FAs disrupts cellular functions and causes lipotoxicity. Thus, by acting hubs for storing excess fat, prevent lipotoxicity preserve homeostasis. LD synthesis turnover have precisely regulated maintain a balanced lipid distribution allow adaptation during stress. Here, we discuss how prolonged exposure lipids affects functions, the roles in buffering stress focusing on

Language: Английский

Citations

17
LDO proteins and Vac8 form a vacuole-lipid droplet contact site to enable starvation-induced lipophagy in yeast DOI Creative Commons
Irene Álvarez-Guerra,

Emma Block,

Filomena Broeskamp

et al.

Developmental Cell, Journal Year: 2024, Volume and Issue: 59(6), P. 759 - 775.e5

Published: Feb. 13, 2024

Lipid droplets (LDs) are fat storage organelles critical for energy and lipid metabolism. Upon nutrient exhaustion, cells consume LDs via gradual lipolysis or lipophagy, the en bloc uptake of into vacuole. Here, we show that dock to vacuolar membrane a contact site is required lipophagy in yeast. The LD-localized LDO proteins carry an intrinsically disordered region directly binds Vac8 form vCLIP, vacuolar-LD site. Nutrient limitation drives vCLIP formation, its inactivation blocks resulting impaired caloric restriction-induced longevity. We establish functional link between microautophagy nucleus, both requiring respective sites upon metabolic stress. In sum, identify tethering machinery find provides platform multiple competing associated with autophagy.

Language: Английский

Citations

11
Microlipophagy from Simple to Complex Eukaryotes DOI Creative Commons

Ravinder Kumar,

Colin Arrowood,

Micah B. Schott

et al.

Cells, Journal Year: 2025, Volume and Issue: 14(2), P. 141 - 141

Published: Jan. 18, 2025

Lipophagy is a selective degradation of lipid droplets in lysosomes or vacuoles. Apart from its role generating energy and free fatty acids for membrane repair, growth, the formation new membranes, lipophagy emerges as key player other cellular processes disease pathogenesis. While fungal, plant, algal cells use microlipophagy, most prominent form animal macrolipophagy. However, recent studies showed that can also microlipophagy to metabolize their droplets. Therefore, no surprise, conserved simple unicellular complex multicellular eukaryotes, many eukaryotic operate both forms lipophagy. Macrolipophagy studied better understood at molecular level, while our understanding very sparse. This review will discuss perspective conservation eukaryotes importance diseases. To appreciate nature different organisms types which has been reported are shown tabular form. We point toward gaps including signaling behind especially organisms.

Language: Английский

Citations

1
Chronic acidosis rewires cancer cell metabolism through PPARα signaling DOI Creative Commons
Michala G. Rolver, Lya Katrine Kauffeldt Holland,

Muthulakshmi Ponniah

et al.

International Journal of Cancer, Journal Year: 2022, Volume and Issue: 152(8), P. 1668 - 1684

Published: Dec. 19, 2022

Abstract The mechanisms linking tumor microenvironment acidosis to disease progression are not understood. Here, we used mammary, pancreatic, and colon cancer cells show that adaptation growth at an extracellular pH (pH e ) mimicking acidic niches is associated with upregulated net acid extrusion capacity elevated intracellular physiological , but . Using metabolic profiling, shotgun lipidomics, imaging biochemical analyses, the adaptation‐induced phenotype characterized by a shift toward oxidative metabolism, increased lipid droplet‐, triacylglycerol‐, peroxisome content mitochondrial hyperfusion. Peroxisome proliferator‐activated receptor‐α ( PPARA PPARα) expression activity upregulated, least in part fatty uptake. PPARα upregulates genes driving peroxisomal mass β‐oxidation capacity, including import proteins CPT1A, CPT2 SLC25A20, electron transport chain components, PEX11A ACOX1, thioredoxin‐interacting protein (TXNIP), negative regulator of glycolysis. This endows acid‐adapted for utilizing acids needs, while limiting As consequence, exhibit sensitivity inhibition. We conclude key upstream changes favoring cell survival niches.

Language: Английский

Citations

35
Role of lipid droplets in neurodegenerative diseases: From pathogenesis to therapeutics DOI Creative Commons

Yubing Kang,

Yee Jie Yeap, Jing Yang

et al.

Neuroscience & Biobehavioral Reviews, Journal Year: 2024, Volume and Issue: 165, P. 105867 - 105867

Published: Aug. 28, 2024

Neurodegenerative diseases (NDDs) are a series of disorders characterized by the progressive loss specific neurons, leading to cognitive and locomotor impairment. NDDs affect millions patients worldwide but lack effective treatments. Dysregulation lipids, particularly accumulation lipid droplets (LDs), is strongly implicated in pathogenesis NDDs. How LDs contribute occurrence development NDDs, their potential as therapeutic targets remain be addressed. In present review, we first introduce processes formation, transportation degradation. We then highlight how contributes cell type-specific manner. Moreover, discuss currently available methods for detecting elaborate on LDs-based strategies Lastly, identify gaps that need filled better leverage LD-based theranostics other diseases. hope this review could shed light role facilitate novel

Language: Английский

Citations

8
Spartin-mediated lipid transfer facilitates lipid droplet turnover DOI
Neng Wan, Zhouping Hong, Matthew AH Parson

et al.

Proceedings of the National Academy of Sciences, Journal Year: 2024, Volume and Issue: 121(3)

Published: Jan. 8, 2024

Lipid droplets (LDs) are organelles critical for energy storage and membrane lipid homeostasis, whose number size carefully regulated in response to cellular conditions. The molecular mechanisms underlying droplet biogenesis degradation, however, not well understood. Troyer syndrome protein spartin (SPG20) supports LD delivery autophagosomes turnover via lipophagy. Here, we characterize as a transfer ability is required degradation. Spartin copurifies with phospholipids neutral lipids from cells transfers vitro its senescence domain. A domain truncation that impairs also while affecting association either LDs or autophagosomes, supporting spartin's physiologically relevant. Our data indicate role spartin-mediated turnover.

Language: Английский

Citations

6
Lipid droplet turnover at the lysosome inhibits growth of hepatocellular carcinoma in a BNIP3-dependent manner DOI Creative Commons
Damián E. Berardi, Althea Bock-Hughes, Alexander R. Terry

et al.

Science Advances, Journal Year: 2022, Volume and Issue: 8(41)

Published: Oct. 12, 2022

Hepatic steatosis is a major etiological factor in hepatocellular carcinoma (HCC), but factors causing lipid accumulation leading to HCC are not understood. We identify BNIP3 (a mitochondrial cargo receptor) as an suppressor that mitigates against attenuate tumor cell growth. Targeted deletion of

Language: Английский

Citations

19